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Experiences and details of a high throughput, multi-user, multiple instrument hardware vendor screening solution for library QC and target purification Mark Bayliss 1 , Joseph Simpkins 1 , Stephane Murphy 1 , Martin Fuhr 2 , Utz-Peter Jagusch 2 , Josephine Archinal 2 , Stefan Oberbörsch 2 (1) Virscidian Inc., 7330 Chapel Hill Road, Suite 201, Raleigh NC 27607, USA (2) Grünenthal GmbH, Zieglestr. 6, 52078 Aachen, Germany Abstract Screening high volumes of analytical results for quality and consistency of results when it comes to library compound management QC, small to medium automated synthesis support and purification of targets is tedious and costly in terms of required experienced manpower. Our laboratories for analyzing incoming samples are comprised of a heterogeneous array of instrument types and instrument vendors. Our goals at the start of the project were multi‐fold. Improve quality of results, reduce the number of false positive results, reduce the number of samples requiring manual reprocessing, and decrease the throughput time from initial QC, purification and post purification QC. Automate the processing of raw data and to create a single consistent output of results that are integrated with our existing inter/intra departmental workflows and corporate infra‐structure. In this presentation we would like to share our practical experiences in achieving our primary goals, some of the challenges that we faced prior to implementing the automated approach and how the new workflow has impacted the departmental workflow in a positive way. Already we have seen the cycle time from initial QC of samples to final QC of purified fractions reduced from multiple days to around 24 hours. The Target of 24 hour turn‐around time for purified compound Historically it has taken some variable number of days to take a crude sample from initial analytical confirmation to a final purified compound that can be used in downstream discovery activities. A systematic analysis of the variability and long lead time resulted in the following observations: • Chemists were having to review 100% of the analytical results at all stages of the process. • A significant percentage of automatically processed results suffered from issues related to baselining, poor integration and poor automated assessment of the presence or absence of the target chemistries. • Significant differences between the results processing and analysis across the different instrument vendors leading to inconsistency in downstream utilization and integration of the results in later workflows and processes. • All these issues led the team to evaluate software and automation solutions from a variety of different industry vendors. Criteria for selection of a vendor solution • Independence of processing across multiple vendors • Quality of final analytical results: • Accuracy of Target assessment. • Accuracy of Area% calculation. • Reliable unattended automation of data processing able to manage 100,000’s of sample analyses annually. • Customization to Grünenthal integration needs . • Integration with our existing infra‐structure. Conclusions Overview This process improvement project has very much been a stepwise project made in close collaboration with Virscidian to fine tune the system details to the workflow requirements of the Grünenthal team at each stage. The current implementation has already reduced total cycle times from a few days to around 24 hours. Quality of Results One of the key benefits that the updated system has delivered has been a major improvement in the quality and accuracy of the automatically calculated results – so much so that the only samples where you may want to do some reintegration are samples that are of poor quality which are almost entirely rejected from further processing and use. As a result of this improvement alone, the confidence of the team in the final results is very high. End‐to‐end process improvements • Cycle times across all parts of the workflow are now reduced significantly especially as the major bottleneck was results reviewing. • Result quality is improved. • Review of data is streamlined and consistent across instrument vendors. • General tools and presentation of the results in streamlined to enable chemists to review results quickly. Detailed information is available when required for the problem samples. • Searching across network folders for raw data, processed data, results, reports and general support files has been almost completely removed from the process as a result of the automated capture and processing of the data by Analytical Studio Express. A knock on effect of this has been to greatly improve the ease of adherence to the entire workflow process. For Further Information www.virscidian.com Contact Joseph Simpkins at [email protected] Contact Mark Bayliss at [email protected] Virscidian Inc. 7330 Chapel Hill Road, Suite 201, Raleigh, NC 27607, USA (919) 809‐7651 or (919) 655 8050 Aiding the Chemist and Analyst review of results The program interface for results review contains a wealth of valuable and relevant information to aide chemist review. Peak Homogeneity Analysis “At‐A‐Glance” Sample Summary Result Review Ranked Categorization of results Plate visualization based on sample purity (%Area) Detailed Isotopic Pattern Matching (Nominal & Accurate Mass) Clear presentation of spectra and chromatograms Useful peak annotation information Workflow Overview Overview Data are analyzed using Analytical Studio Express Server (ASExpress) which reads and processes raw data from the instrument after the acquisition process is completed. All results , processed data, ASR files (RPT like files) and meta data are all managed by ASExpress . Access is made using a search from within Analytical Studio Reviewer (Chemists) and Analytical Studio Professional (Analysts). Phase 1 ‐ Synthesis Synthesis samples may come from both traditional synthesis and automated synthesis robots. These samples are screened by LC/MS for the presence of the target compound and its purity (Area%). During the review of these samples, they are evaluated automatically for the trigger thresholds for purification using a customized plug‐in as part of Analytical Studio Reviewer. Phase 2 ‐ Purification Post purified fractions maybe analyzed to confirm which of the fractions contains the target material which is the most concentrated, however the output fraction information is usually sufficient to allow the post fraction QC process to continue without interruption of data review. Phase 3 – Post Purification QC The dried down fractions containing the purified target compounds are analyzed to confirm that the target compound is still present and that the purity (%Area) of the samples meets or exceeds the corporate requirements for downstream activity and compound storage.
